Despite the widespread appreciation that the prefrontal cortex (PFC) is necessary for flexible action and efficient perception, there is a fundamental gap in understanding the control mechanisms by which it accomplishes these goals. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of executive control. The long-term goal is to understand the mechanisms by which the PFC exerts control over motor and sensory systems. The objective of the current proposal is to test a new model of how activity in the PFC forms maps of prioritized space that tag salient and relevant locations in the visual field, which can then be used as the basis of executive control signals. The mechanisms of bias are likely to involve mechanisms used for saccade planning. The central aim of the project is to test the extent to which the patterns of neural activity in the human PFC are consistent with predictions from the priority map theory, including the functional organization of priority maps, the nature of what is prioritized, and the effects of read-out of priority maps. The rationale for the proposed research is that a better understanding of how the PFC exerts control will lead to a strong theoretical framework within which strategies for the understanding of mental disease will develop. The objective will be to test, refine, and possibly refute, tenets of the priority map theory which will be accomplished by pursuing three specific aims: 1) Identify candidate areas in frontal cortex that show the hallmark feature of priority maps - a spatial topographic organization;2) Test if activity in candidate priority maps is a fundamental and general mechanism used by a variety of spatial cognitions;and 3) Determine how the read out of priority maps sculpts activity in early visual cortex. Strong preliminary data demonstrate the feasibility of project aims in the applicant's hands. Under aim 1, two candidate priority maps were identified in PFC using novel and optimized topographical mapping approaches. Under aim 2, both delay period activity and multivariate patterns of brain activity in candidate priority maps were remarkably similar, if not interchangeable, across a variety of spatial cognition tasks (e.g., memory, attention, planning). Under aim 3, spatially specific persistent activity in candidate priority maps was concomitant with activity in retinotopically matched early visual areas (i.e., V1, V2, V3) suggesting that activity in candidate priority maps guides visual selection via its biasing of activity in early visual areas. The approach is innovative because it is highly programmatic;uses novel approaches to combat individual differences in the functional neuroanatomy of the PFC;and it uses powerful new analytic methods in creative ways to rigorously test key hypotheses. The proposed research is significant because it is expected to test an important new model of executive control and will provide a detailed understanding of the mechanisms by which the human PFC exerts control, such that models of dysfunction of these mechanisms can be targeted as the causes of and potential treatments for neuropathology. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which the prefrontal cortex exerts executive control in the normal brain is necessary to illuminate the mechanisms that could go awry in the pathological brain. Specifically, the proposed research is relevant to NIH's mission because is expected to advance a stronger theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.